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					                                                                                             common carboxyl terminal pentapeptide sequence (V-W-X-Y-Z-COO')
                                                                                Gastrin/CCK
                                                                                             differ significantly only in mammals
                                                                                             G cells of antrum (apical surfaces w/ microvilli allow sampling of lumen); some in duodenum
                                                                                             stimulate gastric acid secretion and gastric growth
                                                                                             101aa pre pro peptide → pro → amidation → active forms G17 and G34
                                                                                             Antrum 90% G17 (nonsulfated form)
                                                                                  Gastrin    Duodenum split btwen G17 and G34
                                                                                             released in antral distention, aa/peptide esposure, and neural stimulation (sight/smell/taste food)
                                                                                             major: stimulates histamine release → binds H2 receptors on parietal cells to stimulate acid secretion
                                                                                             minor: direct stimulation of parietal cells via Gastrin/CCK-B receptors on parietal cell
                                                                                             thanks to SOMATOSTATIN gastric acid in lumen (-) feedback; no gastrin response to peptides at pH < 3
                                                                                             I cells of duodenum
                                                                                             stimulates pancreatic secretion/ gall bladder contraction
                                                                                             response to meal rich in protein/fat
                                                                                   CCK         inhibits directly via pyloric CCK-A receptors
                                                                                                gastric indirectly via CCK-A vagal receptors which in turn decrease gastric motility
                                                                                              emptying SATIETY FACTOR
                                                                                             inhibits gastric secretion by stimulating somatostatin via CCK-A receptors on D cells
                                                                                             antral D cells and neurons
GTP binding G protein; as a rule have seven hydrophobic transmembrane domains




                                                                                                           inhibits gastrin from G cells
                                                                                             stimulated
                                                                                                           inhibits histamine from enterochromaffin like (ECL) cells
                                                                                              by low pH
                                                                                                           directly inhibiting parietal acid secretion
                                                                                Somatostatin
                                                                                             pancreas - inhibits insulin, glucagon, PP and pancreatic exocrine secretion
                                                                                             GI - inhibits gastrin, secretin, CCK, GIP, VIP and motilin
                                                                                             inhibits gut motility and splanchnic blood flow
                                                                                             Octreotide (b/c somatostatin only has 2-3 min half life) used to treat neuroendocrine tumors, secretory diarrh
                                                                                             Parietal cells
                                                                                             initial elevation of intracellular calcium and cAMP
                                                                                   Acid
                                                                                             → activation of protein kinase cascades
                                                                                             → translocation/insertion of H+, K-ATPase into apical plasma membrane
                                                                                             S cells of villous and upper crypt regions of small intestine (primarily duodenum)
                                                                                             stimulated by endogenous HCl
                                                                                  Secretin stimulates alkaline buffering of acid load via bicarbonate rich fluid from pancreas and biliary tree
                                                                                             also inhibits acid secretion and slows gastric emptying
                                                                                             potentiates CCK by stimulating pancreatic enzyme secretion
                                                                                                           L cells
                                                                                                                 xis




                                                                                                           gut produces more glucagon gene products than pancreas, but very little glucagon (alternate s
                                                                                                               ra




                                                                                                  GLP
                                                                                                           functions during feeding to stimulate insulin release to lower blood glucose levels
                                                                                          ula




                                                                                                           stimulated particularly by glucose rich meal but not intravenous glucose
                                                                                     ins




                                                                                                           duodenum and proximal jejunum
                                                                                     o
                                                                                  ter




                                                                                                  GIP      insulinotropic agent (release and synthesis)
                                                                                en




                                                                                                           amplifies effect of insulin on target tissues
                                                                                             28 aa similar to secretin
                                                                                             released from enteric nerves throughout GI tract under VAGAL CONTROL
                                                                                    VIP      receptors in pancreatic acini, pancreatic/biliary ductal epithelial cells, gastric/intestinal epithelial cells/smooth
                                                                                             pancreatic secretion, GI motility, sphincter relaxation, ↑intestinal secretion, ↓gastric secretion, modification of
                                                                                             VIPoma causes watery diarrhea-hypokalemia-achlorydia syndrome (aka Verner Morrison syndrome)
                                                                                             General       extensive homolgy w/in C-terminal domain (PP FOLD)
                                                                                                           expression restricted to endocrine cells
                                                                                         creatic Polypeptide Family




                                                                                                           PP islet cells (less than 10% of islet cells)
                                                                                                  PP
                                                                                                           induced by meal intake; cephalic vagal phase, gastric phase (distention of stomach) and intestina
                                                                                                           high plasma levels in pts with GI endocrine tumors
GTP bindi



            Pancreatic Polypeptide Family
                             neurons and endocrine cells
                             response to a meal (primarily fat)
                    PYY      inhibits GI motility, pancreatic/gastric secretion, and intestinal chloride secretion
                             markedly enhanced in pts with malabsorption ( delay in gastric emptying and intestinal transit a
                             mediator of ileal brake (injection of fat into ilieum/colon slows intestinal transit)
                             neurons
                             regulation of vascular and cardiac response (vasoconstrictive), circadian rhythm, and potent stim
                   NPY
                             released after sympathetic stimulation and enteral feedings
                             inhibitory effects include decreaseing intestinal and pancreatic secretion, slowing GI motility and c
                most prominent member of Tachykinin peptide family
                neurons of esophagus, duodenum, and colon
   Substance P
                stimulates esophageal and intestinal peristalsis, pancreatic secretion and blood flow in the gut
                mediates pain from gut
                M cells of duodenum and proximal jejunum
       Motilin  secreted into circulation in cyclic manner (correlated with antroduodenal motor activity during fasting i.e. inter
       Family   exogenous motilin accelerates gastric emptying of meal
                Erythromycin is a motilin receptor agonist
                single transmembrane receptor (unlike Gprotein coupled receptors above) w/ ligand binding trigerring protein
Tyrosine Kinase epithelial growth factor (EGF), insulin like growth factor (IGF), platelet derived growth factor (PDGF), fibrobla
Receptor Family prominent effect on cell growth (really?!)
                affect cell survival, differentiation and movement
 in duodenum




 /smell/taste food)
stimulate acid secretion

ponse to peptides at pH < 3




ocrine tumors, secretory diarrhea, acromegaly, and symptoms of portal hypertension




as and biliary tree



y little glucagon (alternate splicing)
glucose levels




estinal epithelial cells/smooth muscle layers, vasular smooth muscle, and lymphocytes
stric secretion, modification of immune function, and GI blood flow
erner Morrison syndrome)



 tion of stomach) and intestinal phase (presence of fat/aa's/glucose in duodenum)
mptying and intestinal transit and increase in digestive and absorptive efficiency)


adian rhythm, and potent stimulus of feeding

etion, slowing GI motility and causing splanchnic vasoconstriction


d flow in the gut


 activity during fasting i.e. interdigestive state - PHASE III of MMC)


 gand binding trigerring protein tyrosine kinases
growth factor (PDGF), fibroblast growth factor (FGF), and transforming growth factor (TGF)
ZE   gastrinoma; unchecked gastrin release
     ulcers
     diarrhea (excess gastric secretion and inactivation of digestive enzymes not used to low pH)
     "wet" stomach look w/ prominent gastric folds (trophic effect of gastrin)
     paradoxical increase of serum gastrin when IV secretin is given
     diff dx - achlorydia e.g in pernicious anemia (no HCl release  unchecked release of gastrin)
     complication - chronic hypergastrinemia can result in ECL hyperplasia/carcinoid tumors
ed to low pH)


ease of gastrin)

				
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posted:11/21/2011
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